Dynamics of Bone Disease Biomarkers Dickkopf-1 and Sclerostin in Patients with Multiple Myeloma

Abstract

Dickkopf-1 (DKK-1) and sclerostin are essential Wnt/β-catenin pathway inhibitors, playing an important role in multiple myeloma bone disease (MBD). We aimed to examine the serum DKK-1 and sclerostin variations in newly diagnosed multiple myeloma (NDMM) patients at diagnosis and in the course of therapy, including autologous stem cell transplantation (ASCT). This study included 41 NDMM-patients and 33 controls. MBD was assessed by whole-body low-dose computed tomography. DKK-1 and sclerostin were assayed by commercial ELISA kits. At diagnosis, NDMM-patients revealed significantly higher DKK-1 and sclerostin values (p < 0.0001), showing dependence on disease stage (lowest in ISS-I and highest in ISS-III: p < 0.0012 and p < 0.025, respectively, for both proteins). Bone lesions revealed significant positive correlation with both DKK-1 (p < 0.05) and sclerostin (p < 0.0001). In the course of therapy, significant reduction, more prominent after ASCT, was observed for both parameters in each treatment point compared to the baseline (p < 0.0001). Markedly lower sclerostin (p < 0.01) and DKK-1 (p < 0.05) values were observed in patients with complete and very good partial response compared to those with partial response, stable, or progressive disease. Sclerostin and DKK-1 in NDMM patients reflect the MBD severity and the effect of therapy. Both proteins could represent a novel tool for better disease monitoring and effectiveness of therapy.

Keywords: Dickkopf-1; multiple myeloma bone disease; sclerostin.

Figure 1

Serum levels of sclerostin and DKK-1 in controls and patients at baseline. Statistical significance was indicated at p < 0.05.

Figure 2

Comparison of serum levels of sclerostin and DKK-1 in NDMM patients, stratified according to the ISS staging system. Statistical significance was indicated at p < 0.05.

Figure 3

Correlations of DKK-1 and sclerostin with Hb, albumin, and B2MG. Hb–hemoglobin; Alb—albumin, Β2MG—ß2 microglobulin. Statistical significance was indicated at p < 0.05.

Figure 4

Serum levels of sclerostin and DKK-1 in NDMM patients stratified by the number of bone lesions. G1—patients with ≤3 osteolytic lesions, G2—patients >3 osteolytic lesions and/or presence of bone fractures. Statistical significance was indicated at p < 0.05.

Figure 5

Serum levels of sclerostin and DKK-1 in NDMM patients, stratified according to BMI by MPCs. BMI—bone marrow infiltration; MPCs—multiple myeloma plasma cells. Statistical significance was indicated at p < 0.05.

Figure 6

Sclerostin and Dickkopf-1 assessed at different time points. T0—at diagnosis; T1—after 4 cycles of chemotherapy; T2—after another 4 cycles (8 cycles) of chemotherapy; TA—after autologous stem cell transplantation. Statistical significance was indicated at p < 0.05.

Figure 7

Sclerostin and Dickkopf-1 according to the treatment response. CR—complete response, VGPR—very good partial response, PR—partial response, SD—stable disease, PD—progressive disease. Statistical significance was indicated at p < 0.05.